NEPL2_CAEEL
ID NEPL2_CAEEL Reviewed; 736 AA.
AC O44857;
DT 07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Neprilysin-2 {ECO:0000312|WormBase:T05A8.4};
DE EC=3.4.24.- {ECO:0000305};
GN Name=nep-2 {ECO:0000312|WormBase:T05A8.4};
GN ORFNames=T05A8.4 {ECO:0000312|WormBase:T05A8.4};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|EMBL:CCD73586.1};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP HIS-571 AND HIS-575.
RX PubMed=20929849; DOI=10.1126/science.1192020;
RA Yamada K., Hirotsu T., Matsuki M., Butcher R.A., Tomioka M., Ishihara T.,
RA Clardy J., Kunitomo H., Iino Y.;
RT "Olfactory plasticity is regulated by pheromonal signaling in
RT Caenorhabditis elegans.";
RL Science 329:1647-1650(2010).
CC -!- FUNCTION: Required for olfactory plasticity, which is the change from
CC positive chemotaxis to dispersal after prolonged exposure to an
CC odorant. Thought to antagonise snet-1 by degrading excess snet-1
CC peptides and thus enabling olfactory plasticity.
CC {ECO:0000269|PubMed:20929849, ECO:0000303|PubMed:20929849}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P08473};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P08473};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type II
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in muscle cells, GLR cells, SMB motor
CC neurons and AIM interneurons. {ECO:0000269|PubMed:20929849}.
CC -!- DISRUPTION PHENOTYPE: Severe defect in olfactory plasticity in response
CC to the odorants benzaldehyde, isoamylalcohol, diacetyl and pyrazine.
CC {ECO:0000269|PubMed:20929849}.
CC -!- SIMILARITY: Belongs to the peptidase M13 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01233}.
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DR EMBL; FO081704; CCD73586.1; -; Genomic_DNA.
DR RefSeq; NP_494343.2; NM_061942.2.
DR AlphaFoldDB; O44857; -.
DR SMR; O44857; -.
DR DIP; DIP-24357N; -.
DR STRING; 6239.T05A8.4; -.
DR MEROPS; M13.015; -.
DR EPD; O44857; -.
DR PaxDb; O44857; -.
DR PeptideAtlas; O44857; -.
DR PRIDE; O44857; -.
DR EnsemblMetazoa; T05A8.4.1; T05A8.4.1; WBGene00020230.
DR GeneID; 188090; -.
DR KEGG; cel:CELE_T05A8.4; -.
DR UCSC; T05A8.4; c. elegans.
DR CTD; 188090; -.
DR WormBase; T05A8.4; CE30162; WBGene00020230; nep-2.
DR eggNOG; KOG3624; Eukaryota.
DR HOGENOM; CLU_006187_4_3_1; -.
DR OMA; APRNHDA; -.
DR OrthoDB; 282463at2759; -.
DR PhylomeDB; O44857; -.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR SignaLink; O44857; -.
DR PRO; PR:O44857; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00020230; Expressed in larva and 3 other tissues.
DR GO; GO:0009986; C:cell surface; IMP:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; TAS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; TAS:UniProtKB.
DR GO; GO:0008355; P:olfactory learning; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:0050920; P:regulation of chemotaxis; IMP:UniProtKB.
DR CDD; cd08662; M13; 1.
DR Gene3D; 1.10.1380.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR000718; Peptidase_M13.
DR InterPro; IPR018497; Peptidase_M13_C.
DR InterPro; IPR042089; Peptidase_M13_dom_2.
DR InterPro; IPR008753; Peptidase_M13_N.
DR PANTHER; PTHR11733; PTHR11733; 1.
DR Pfam; PF01431; Peptidase_M13; 1.
DR Pfam; PF05649; Peptidase_M13_N; 1.
DR PRINTS; PR00786; NEPRILYSIN.
DR PROSITE; PS51885; NEPRILYSIN; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Disulfide bond; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..736
FT /note="Neprilysin-2"
FT /id="PRO_0000431419"
FT TOPO_DOM 1..19
FT /note="Cytoplasmic"
FT TRANSMEM 20..40
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 41..736
FT /note="Extracellular"
FT DOMAIN 52..736
FT /note="Peptidase M13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT COILED 103..123
FT /evidence="ECO:0000255"
FT ACT_SITE 572
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT ACT_SITE 637
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT BINDING 571
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT BINDING 575
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT BINDING 633
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 53..58
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 76..721
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 84..681
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 142..399
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 608..733
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT MUTAGEN 571
FT /note="H->F: Fails to rescue the nep-2 olfactory plasticity
FT defect, suggesting that peptidase activity is required for
FT olfactory plasticity; when associated with F-575."
FT /evidence="ECO:0000269|PubMed:20929849"
FT MUTAGEN 575
FT /note="H->F: Fails to rescue the nep-2 olfactory plasticity
FT defect, suggesting that peptidase activity is required for
FT olfactory plasticity; when associated with F-571."
FT /evidence="ECO:0000269|PubMed:20929849"
SQ SEQUENCE 736 AA; 85422 MW; 5B55DD364EF2F2B9 CRC64;
MRPDEEDGTT KSPGSRWTRI WAIIALILLI LFLLVLGAAI YFYINYKDSS DVCLSPGCIK
TASVILSSMN SSVDPCDDFY EFACGQWIKG HPIPDDAPSV SNFENLGQDL EFALKELLDE
NDEPYDYETS AVGKAKYFYN LCLNESEILD NWRTTFDEVV KSFGGWPSLG HQMKPDASIE
MLYADMVAKF KADSLFKATV QPDDKNSQRH VLLIDQPQLN LFARDFYVAA ENEERMAYLQ
LIRDVLILLD ADRTRATLDA KEIIDFETAL ANITMADEHR HDIAELYTKI TLGEMRRSLP
HFNWPLFFNR MFKDLHEKNG KRITFDDNTE VVVYGYEFLR RLDVLIPQYD NRLIVNYLEW
CWFFKTMLRD LPDPFALTIF KFYKTLNIMN VQKVRWHGCV TRINSLMPMA TSAIYVKNHF
DHEAKQQVEE MISLIMESFV DLLLSEDWLT KETKQTAKQK VNEMKRKIGY PDYLNDPAAV
NNEYKTFKVY PGHYYQTKFS FYEQYQRDVL ERITEAVDRE RWVAGAALVN AFYSPNTNEI
IFPAGILQPV FYSKDFPSSM NFGGIGVVIG HEITHGFDDR GRLYDNLGNI RQWWDNATIS
KFEHKAQCIE KQYSSYVLDQ INMQINGKST KGENIADNGG LKQAYRAYKK YEKRHSRPPR
LPGVNLTHDQ LFFLNYAQIW CGTMNDKEAI RKLRTSEHSP GPIRVKGPLS NSYDFAKAYN
CEPGSQMNPR EKCRVW
